The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Intravenous High-Dose Selenium Supplementation in Patients with Systemic Inflammatory Response Syndrome: A Pilot Study

고용량 셀레늄 투여가 전신 염증 반응 증후군에 미치는 영향: 예비 보고

  • Kim, Mi-Jeoung (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Lee, Ki-Jong (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Oh, In-Myung (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Oh, Dong-Hyun (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Yoo, Kyoung-Hwa (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Park, Ju-Sang (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Jang, Eun-Jeong (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Park, Sang-Jong (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Park, Sang-Woon (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Kim, Sang-Jung (Department of Internal Medicine, Bundang Jesaeng Hospital) ;
  • Baik, Hyun Wook (Department of Internal Medicine, Bundang Jesaeng Hospital)
  • Received : 2012.01.13
  • Accepted : 2012.10.16
  • Published : 2013.04.01
⟨ Previous Next ⟩

Abstract

Background/Aims: Systemic inflammatory response syndrome (SIRS) can induce occurrence of oxidative stress. Several reports have evaluated selenium supplementation in SIRS patients with encouraging results. Therefore, we evaluated the effect of intravenous high-dose selenium supplementation in patients with SIRS. Methods: Patients were randomly assigned to one of two groups: the selenium group (800 ${\mu}g/day$ of selenoic acid by intravenous bolus injection for 7 days) or the placebo group. Physical and biochemical measurements were used to assay acute phase reactants, severity of illness index and serum selenium concentration. Results: A total of 23 patients classified as mild-to-moderate severity of illness index were enrolled between March 2010 and October 2011. Serum selenium concentration increased in the selenium group after intervention, but there was no significant change in the placebo group. In the selenium group, the white blood cell (WBC) count, serum level of c-reactive protein (CRP), Acute Physiology and Chronic Health Evaluation II (APACHEII) score and Sequential Organ Failure Assessment (SOFA) score improved significantly by days 7 and 14 compared with day 0. In the placebo group, only the serum CRP level at day 14 and APACHE II score at days 7 and 14 improved significantly compared to day 0. Conclusions: Intravenous supplementation with high-dose selenium improved acute phase reactants and the severity of illness index in patients with SIRS. However, larger prospective clinical trials are required to determine the efficacy of selenium supplementation in SIRS patients.

목적: 전신염증반응증후군과 패혈증에 빠지면 과도한 산화성 스트레스가 발생한다. 고용량 셀레늄 정맥내 투여가 인체의 염증 조절 작용을 보완하여 일부 전신염증반응증후군 및 패혈증 환자의 예후에 영향을 미친다는 보고가 있어 본 연구에서는 전신염증반응증후군 환자에게 고용량 셀레늄을 정맥내 투여할 경우의 효과에 대해 알아보고자 하였다. 방법: 대상 환자들은 무작위로 셀레늄군 또는 대조군으로 분류하였고, 셀레늄군에 1주일간 매일 셀레늄 800 ${\mu}g$을 30분에 걸쳐 정맥내 일시주사하였고, 대조군에는 생리 식염수를 주사하였다. 급성기 반응물질과 질환 중증도지표가 호전되는 속도를 비교하기 위하여 진찰 및 혈액 검사를 시행하였다. 결과: 2010년 3월부터 2011년 8월까지 경증 전신염증반응증후군 환자와 중등증 전신염증반응증후군 환자 23명이 등록되었다. 셀레늄군의 혈청 셀레늄 농도는 시험 0일 9.95 ${\mu}g/dL$에서 시험 7일 18.15 ${\mu}g/dL$로 유의하게 호전되었으나(p = 0.005), 대조군의 혈청 셀레늄 농도는 시험 0일에 비해 시험 7일에 유의한 변화가 없었다(p = 1.000). 백혈구 수와 SOFA 점수는 셀레늄군에서 시험 0일에 비하여 시험 7일과 시험 14일에 유의한 호전을 보였으나 대조군에서는 시험 7일과 시험 14일 모두 유의한 호전이 없었다. 혈청 CRP 수치는 셀레늄군에서 시험 0일에 비하여 시험 7일과 시험 14일에 유의하게 호전을 보였으나 대조군에서는 시험 7일에는 유의한 호전이 없었고, 시험 14일에 유의한 호전을 보였다. APACHEII (Acute Physiology and Chronic Health Evaluation II) 점수는 셀레늄군과 대조군 모두에서 시험 0일에 비하여 시험 7일과 시험 14일에 유의한 호전을 보였다. 셀레늄 투여와 연관된 특별한 부작용은 관찰되지 않았다. 결론: 경증 전신염증반응증후군 환자와 중등증 전신염증반응증후군 환자에 고용량 셀레늄 정맥내 일시주사는 일부 급성기 반응물질 및 질환중증도지표를 호전키는 효과가 있다. 그러나 본 연구는 대상자의 수가 적고, 이중 눈가림 방법이 사용되지 않아 편견의 가능성이 있으며, 투약의 효과지표로 급성기 반응물질과 질환중증도지표만을 모니터하였고, 7일 사망률, 28일 사망률 등 예후지표를 보지 않았다는 한계점이 있어 향후 대규모 연구의 필요성을 환기시키는 점에 그 의의가 있다고 판단된다.

Keywords

References

  1. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709. https://doi.org/10.1056/NEJM200103083441001
  2. Engel C, Brunkhorst FM, Bone HG, et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med 2007;33:606-618. https://doi.org/10.1007/s00134-006-0517-7
  3. Annane D, Aegerter P, Jars-Guincestre MC, Guidet B; CUB-Rea Network. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med 2003; 168:165-172. https://doi.org/10.1164/rccm.2201087
  4. Mishra V. Oxidative stress and role of antioxidant supplementation in critical illness. Clin Lab 2007;53:199-209.
  5. Bulger EM, Maier RV. Antioxidants in critical illness. Arch Surg 2001;136:1201-1207. https://doi.org/10.1001/archsurg.136.10.1201
  6. Goode HF, Webster NR. Free radicals and antioxidants in sepsis. Crit Care Med 1993;21:1770-1776. https://doi.org/10.1097/00003246-199311000-00029
  7. Berger MM. Can oxidative damage be treated nutritionally? Clin Nutr 2005;24:172-183. https://doi.org/10.1016/j.clnu.2004.10.003
  8. Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med 2005;31:327-337. https://doi.org/10.1007/s00134-004-2522-z
  9. Forceville X, van Antwerpen P. Selenocompounds and selenium: a biochemical approach to sepsis. In: Vincent JL, ed. 2008 Yearbook in Intensive Care and Emergency Medicine. Berlin: Springer-Verlag, 2008:454-466.
  10. Burk RF, Hill KE. Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. Annu Rev Nutr 2005;25:215-235. https://doi.org/10.1146/annurev.nutr.24.012003.132120
  11. Papp LV, Lu J, Holmgren A, Khanna KK. From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal 2007;9:775-806. https://doi.org/10.1089/ars.2007.1528
  12. Kim JY. Antioxidants in Sepsis. Korean J Crit Care Med 2010;25:57-60. https://doi.org/10.4266/kjccm.2010.25.2.57
  13. Crimi E, Sica V, Williams-Ignarro S, et al. The role of oxidative stress in adult critical care. Free Radic Biol Med 2006;40:398-406. https://doi.org/10.1016/j.freeradbiomed.2005.10.054
  14. Goodyear-Bruch C, Pierce JD. Oxidative stress in critically ill patients. Am J Crit Care 2002;11:543-551.
  15. Sakr Y, Reinhart K, Bloos F, et al. Time course and relationship between plasma selenium concentrations, systemic inflammatory response, sepsis, and multiorgan failure. Br J Anaesth 2007;98:775-784. https://doi.org/10.1093/bja/aem091
  16. Stawicki SP, Lyons M, Aloupis M, Sarani B. Current evidence from phase III clinical trials of selenium supplementation in critically Ill patients: why should we bother? Mini Rev Med Chem 2007;7:693-699. https://doi.org/10.2174/138955707781024526
  17. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864-874. https://doi.org/10.1097/00003246-199206000-00025
  18. Dolph L. Hatfield, Marla J. Berry, Vadim N. Glasdyshev. Selenium: a historical perspective. In: James E. Oldfield. Selenium: Its Molecular Biology and Role in Human Health. 2nd ed. New York: Springer Science + Business Media, LLC, 2006.
  19. Brown KM, Arthur JR. Selenium, selenoproteins and human health: a review. Public Health Nutr 2001;4:593-599.
  20. Kohrle J. The deiodinase family: selenoenzymes regulating thyroid hormone availability and action. Cell Mol Life Sci 2000;57:1853-1563. https://doi.org/10.1007/PL00000667
  21. Rayman MP. The importance of selenium to human health. Lancet 2000;356:233-241. https://doi.org/10.1016/S0140-6736(00)02490-9
  22. Geoghegan M, McAuley D, Eaton S, Powell-Tuck J. Selenium in critical illness. Curr Opin Crit Care 2006;12:- 136-141.
  23. Angstwurm MW, Engelmann L, Zimmermann T, et al. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med 2007;35: 118-126. https://doi.org/10.1097/01.CCM.0000251124.83436.0E
  24. Mishra V, Baines M, Perry SE, et al. Effect of selenium supplementation on biochemical markers and outcome in critically ill patients. Clin Nutr 2007;26:41-50. https://doi.org/10.1016/j.clnu.2006.10.003
  25. Martindale RG, McClave SA, Vanek VW, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: executive summary. Crit Care Med 2009; 37:1757-1761. https://doi.org/10.1097/CCM.0b013e3181a40116
  26. Singer P, Berger MM, Van den Berghe G, et al. ESPEN Guidelines on Parenteral Nutrition: intensive care. Clin Nutr 2009;28:387-400. https://doi.org/10.1016/j.clnu.2009.04.024
  27. World Health Organization. Selenium [Internet]. Sungnam (KR): World Health Organization, c2012 [cited 2011 Dec 20]. Available from: http://whqlibdoc.who.int/publications/ 2004/9241546123_chap10.pdf.
  28. Forceville X, Laviolle B, Annane D, et al. Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit Care 2007;11:R73. https://doi.org/10.1186/cc5960
  29. Valenta J, Brodska H, Drabek T, Hendl J, Kazda A. Highdose selenium substitution in sepsis: a prospective randomized clinical trial. Intensive Care Med 2011;37:808-815. https://doi.org/10.1007/s00134-011-2153-0
  30. Angstwurm MW, Gaertner R. Practicalities of selenium supplementation in critically ill patients. Curr Opin Clin Nutr Metab Care 2006;9:233-238. https://doi.org/10.1097/01.mco.0000222105.30795.7f
  31. Manzanares Castro W. Selenium in critically ill patients with systemic inflammatory response. Nutr Hosp 2007;22: 295-306.
  32. Wang Z, Forceville X, Van Antwerpen P, et al. A large-bolus injection, but not continuous infusion of sodium selenite improves outcome in peritonitis. Shock 2009;32:140-146. https://doi.org/10.1097/SHK.0b013e318193c35d
  33. Yang G, Yin S, Zhou R, et al. Studies of safe maximal daily dietary Se-intake in a seleniferous area in China: part II. relation between Se-intake and the manifestation of clinical signs and certain biochemical alterations in blood and urine. J Trace Elem Electrolytes Health Dis 1989;3:123-130.
  34. Valenta J, Brodska H, Drabek T, Hendl J, Kazda A. High-dose selenium substitution in sepsis: a prospective randomized clinical trial. Intensive Care Med 2011;37: 808-815. https://doi.org/10.1007/s00134-011-2153-0
  35. Manzanares W, Biestro A, Torre MH, Galusso F, Facchin G, Hardy G. High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation. Intensive Care Med 2011;37: 1120-1127. https://doi.org/10.1007/s00134-011-2212-6
  36. Tietz NW. Clinical Guide to Laboratory Tests. Philadelphia: WB Saunders Co., 1983.
  37. Lee O, Moon J, Chung Y. Assessment of selenium status in adult females according to life cycle. Korean J Nutr 2003; 36:491-499.